The Neurocritic

Sunday, November 30, 2008

...is the title of a book by Thea Hillman, in which (according to a review by David S. Hall),

She speaks of her experiences as a young child, being diagnosed with Congenital Adrenal Hyperplasia, and what that experience meant to a four year old girl who was growing pubic hairs, a child who was poked and examined by many doctors, and had a total lack of personal privacy of her body. She comes back to this experience many times in the stories she tells of her life as a person who does not really know what gender she is.

is characterized by severe androgen excess beginning in the fetus. In about 95% of patients CAH is caused by a defect in the 21-hydroxylase gene (CYP21), leading to an impaired synthesis of cortisol["stress hormone" produced by the adrenal gland] and aldosterone[hormone that causes the kidneys to retain sodium and water]. The low cortisol level triggers an increased production of adrenocorticotropic hormone, resulting in hyperplasia of the adrenal glands with increased synthesis of steroid precursors and elevation of androgen levels. The androgen excess is present from early embryogenesis, and causes in girls varying degrees of virilization of the external genitalia, depending on the degree of enzyme deficiency.

Ciumas et al. wanted to investigate whether fetal testosterone exposure is the major underlying mechanism for sexual dimorphism in the human brain. In particular, sex differences in the anatomy and physiology of the hypothalamus and the amygdala were of interest. Thus, they turned to adult women with CAH, since

She speaks of her mother's prayers that she would be normal. She speaks of normal this way:

"I take the war on terror personally because the war on terror is really a war on difference, because my body strikes terror in the hearts of other Americans.

"My body and the bodies of the people I love are the most intimate sites of American imperialism. Because our sex anatomy isn't normal, they operate on us without our consent. Because who we have sex with isn't normal, they won't let us get married. Because our gender isn't normal, they don't give us jobs, health care, or housing. We work, we pay rent, we pay taxes, but because we're not normal, we don't get the same freedoms other Americans enjoy, the same freedoms American soldiers are murdering to protect."

The study, which was not conducted in America but in Sweden by Dr. Ivanka Savic Berglund's group1 at the prestigious Karolinska Institute, was a continuation of their work on sex hormones and olfaction. Previously (Savic et al., 2001), they demonstrated that heterosexual men (HeM) and heterosexual women (HeW) showed different hypothalamic responses to smelling the putative pheromones, androstadienone (AND) and estratetraenol (EST). Specifically they used PET (positron emission tomography) to measure changes in cerebral blood flow responses to inhaling various odorants, which included sex steroids, butanol, cedar oil, lavender oil, and eugenol (clove). EST induced activity in the hypothalamus of HeM but in olfactory regions of HeW. Conversely, AND induced activity in the hypothalamus of HeW but in olfactory regions of HeM, which is not too surprising if these substances are, in fact, pheromones. The opposite sex pheromone is not processed like a regular scent, whereas the same sex pheromone is.

Furthermore, they also examined hypothalamic responses to these putative pheromones in gay men (Savic et al., 2005) and lesbians (Berglund et al., 2006). In the first experiment, the comparison of gay men, straight men, and straight women was pretty straightforward (so to speak). HeM and HeW scored as 0 on the Kinsey scale (exclusively heterosexual), and the gay male subjects scored as 6 (exclusively homosexual). The results were as expected: the hypothalami of gay men were activated by AND, not EST (which was treated like any other odor). The results from the second experiment were less than straightforward. The lesbian group (between 5 and 6) did not look "just like straight men." Instead,

...the lesbian subjects did not show a differentiated pattern of activation with AND and EST; they engaged the amygdala and the piriform and the insular cortices (the classical odor-processing circuits) when smelling both of these compounds.

As a consolation prize, however, the lesbians were unlike HeW (since AND didn't turn on their hypothalami) and somewhat like HeM (since EST activated one overlapping region of the hypothalamus at a lower statistical threshold). [For more info on this study, see Sweat, Urine, and Sexual Orientation and The PNAS Word.]

That brings us to the present experiment. As you might guess, the question was whether CAH women looked more like HeM than HeW when sniffing the steroids.

Is that what they found?

Despite the genetically verified diagnosis and parental reports about boy-typical play behavior during childhood, the pattern of activation in the presently investigated CAH women was remarkably similar to that of female controls, and different from the pattern of male controls. CAH women and HeW activated the anterior hypothalamus with AND, whereas HeM activated this region with EST. Furthermore, whilst the amygdala connectivity differed between the male and female controls, no difference was observed between control females and CAH females. Thus, both with respect to aspects of functional organization and functional activation of the limbic circuits CAH women showed a pattern congruent with their biological sex, and different from the opposite sex. Our hypothesis that these specific aspects of cerebral dimorphism would have masculine features in CAH women was thereby rejected.

So no, it was not what they found.

Figure 1 (Ciumas et al., 2008). Illustration of group-specific activations with putative pheromones and odors. The Sokoloff's color scale illustrates Z values reflecting the degree of activation. As the same brain section is chosen, the figures do not always illustrate maximal activation for each condition. Clusters of activated regions are superimposed on the standard brain MRI, midsagittal plane.

This failure to show a difference between CAH women and control women was obtained even though the two groups were not particularly well-matched for sexual orientation! [a glaring weakness that could have been rectified by recruiting a few bisexual control women]. Eight of the CAH women rated as Kinsey 0, but three others rated as 2, 4, and 5.2

At any rate, these results provide no support for the notion that exposure to high levels of fetal testosterone will result in the "masculinization" of sexually dimorphic limbic circuits. Why? What does this have to say about fetal testosterone and the "male brain" view of development (e.g., Christine Knickmeyer & Baron-Cohen, 2006)? Ciumus et al. were puzzled, but offered the following speculations:

Explanations to these discrepancies are not evident from the present data. We can only conclude that intrauterine virilization of genitalia is not necessarily paralleled by a masculinization of the limbic brain, at least not with respect to signal response to AND and EST, and the baseline amygdala connectivity, which are 2 indices of sex-dimorphism. It is theoretically possible that various sex dimorphic features are affected by fetal testosterone in a dose dependent manner. Whilst such a scenario could be attributed for the differences between HeM and HeW (with extremely high testosterone levels in male fetuses), it is less likely to explain the "male" like AND and EST activation and functional connectivity in lesbian women described in our previous studies. None of our lesbian participants in these studies had genital masculinization, which is expected already at moderate elevations of fetal testosterone. An alternative possibility is that various sex dimorphic features may have different etiological factors; in this respect recent studies by Arnolds group at UCLA are of particular interest as they indicate existence of early, and testosterone-independent chromosomal effects on the brain. Finally, several different etiological factors could contribute to a same sexually dimorphic cerebral feature, for example, psychosexual outcome. The 3 alternatives are not mutually exclusive. Although presently speculative, in the view of present results they all seem relevant to address in the near future.

So there's no neat conclusion, only ambiguity. The calls for future studies are issued. But where does it all fit, in the grand scientific scheme of things? In the less grandiose human scale of things, to be different and yet not-so-different? When talking about her participation in the Intersex and Transgender communities, Thea Hillman says:

"I fear that regardless of the fact that I've been hormonally altered since age six in order to achieve and maintain a mythical gender ideal, I can't safely talk about my concerns about hormones and surgery in our community for fear of being seen as anti-trans and anti-surgery."

Footnotes

1 In the recent past, The Neurocritic (and other neuropundits) have been critical of Savic's work on cerebral asymmetry and sexual orientation, but we'll put that aside for today.

2 Another potential source of variability was the severity of the condition, which ranged from 1 to 5 (least to most severe), with a mean value of 3.18 in the 11 participants. Only four of the CAH women rated a severity of 4 or 5, so this might have obscured potential group differences in the data.

Active masculinization by fetal testosterone is believed to be a major factor behind sex differentiation of the brain. We tested this hypothesis in a 15O-H2O positron emission tomography study of 11 women with congenital adrenal hyperplasia (CAH), a condition with high fetal testosterone, and 26 controls. Two indices of cerebral dimorphism were measured—functional connectivity and cerebral activation by 2 putative pheromones (androstadienone [AND] and estratetraenol [EST]), previously reported to activate the hypothalamic networks in a sex-differentiated manner. Smelling of unscented air was the baseline condition, also used for measurements of functional connectivity from the amygdala. In CAH women and control women AND activated the anterior hypothalamus, and EST the amygdala, piriform, and anterior insular cortex. The pattern was reciprocal in the male controls. Also the functional connections were similar in CAH women and control women, but different in control men. Women displayed connections with the contralateral amygdala, cingulate, and the hypothalamus, men with the basal ganglia, the insular and the sensorimotor cortex. Furthermore, the connections were in CAH and control women more widespread from the left amygdala, in men from the right amygdala. Thus, we find no evidence for masculinization of the limbic circuits in women with high fetal testosterone.

"Normal is a weapon of mass destruction.It's just as deadly, and just like those weapons,it'll never be found."

I must admit a certain morbid fascination with how one of my favorite streams of thought — embodied cognition — would fare combined with cultural evolution — an area of scholarship that, well, to put it nicely, is uneven (before you get all defensive, let me just stop you with one word: mimetics). It’s sort of like watching one of your good friends get hit on by a sleazy guy at a bar. She looks happy, but you’re sort of cringing at the chance that she might actually take him home. In spite of this instinctual cringe, this special edition of Philosophical Transactions has some really interesting work on cultural evolution, especially because many of the pieces focus tightly on the enormously problematic issue of cultural transmission.

And the result of this tawdry hook up is commendable, according to Greg:

...Wheeler and Clark map out a path toward reconciliation between evolutionary theory and interest in the brain that isn’t the same one — massive modularity, instinct, universal grammar, etc. — that seems now to be so out of step with both contemporary evolutionary theory and brain sciences. The result is really outstanding and thought provoking, and I can’t recommend the article highly enough if you can get your hands on it. [I couldn't.]

Sunday, November 23, 2008

The Neurocritic was perhaps a little harsh1 on New Scientist in the previous post about The Female Macaque Brain. My complaints were with use of the words "gossip" and "gossipy" to describe the vocalizations of rhesus monkeys, and with mention of the stereotype "women are the chattier sex" without directly rebutting it.2

The female brain has a clever way of mitigating the stress experienced during menstruation: it flip-flops.

The region of the brain used for coping with stress flips to the opposite side of the brain during a woman's period - from an area linked to negative emotion to one that usually deals with cheerier thoughts.

This story is so much better! Because we want to associate the female brain during menstruation with either waffling and indecision, or turning somersaults. But it seems like all this brain flipping is helpful:

Such a change could help women cope with the hormonal maelstrom going on in their bodies without causing huge behavioural shifts. Oestrogen levels levels, in particular, plummet around menstruation.

Now of course, the use of hyperbolic language to describe a change in the relative hemispheric asymmetry of MEG activity in prefrontal cortex is in no way designed to draw readers to what might otherwise be an esoteric research finding.3

OK. So the actual paper (Hwang et al., 2008b) expanded upon an earlier body of work suggesting that the left and right prefrontal cortices are part of separate neural systems involved in approach- and withdrawal-related emotions, respectively (Davidson et al., 2000). This view was initially based on brain lesion studies, with more recent evidence coming from electroencephalographic recordings. Broadly speaking, strokes and other injuries to the left frontal lobe more often lead to depression, because one of the regions associated with positive emotions is no longer intact. Conversely, damage to the right frontal lobe can lead to anosognosia, or denial of impairment, because a region associated with negative emotions is no longer intact. In the EEG realm, the evidence consists of frontal asymmetries in activity during positive and negative states. Spectral power in the alpha frequency band (8-12 Hz) is used as a measure of cortical activation, with reduced alpha power associated with greater activation. Although the evidence isn't entirely clear on this point, a baseline L>R frontal EEG asymmetry has been associated with a better coping style in response to stress.

Here's where the studies of Hwang and colleagues enter the scene. An earlier paper (Hwang et al., 2008a) looked at resting baseline frontal MEG asymmetries in women during two points of the menstrual cycle: the peri-ovulatory (OV) and menstrual (MC) phases:

Difference in spontaneous frontal alpha asymmetry pattern across the menstrual cycle was also noted. Relatively higher right frontal activity was found during the OV phase; relatively higher left frontal activity was noted during the MC phase. The alteration of frontal alpha asymmetry might serve a sub-clinical correlate for hormonal modulation effect on dynamic brain organization for the predisposition and conceptualization of different affective styles across the menstrual cycle.

This result seems counter-intuitive initially, because higher levels of estrogen (as during OV) are thought to increase approach behaviors and motivations, which would presumably be associated with greater left than right frontal activity. Contrary to this, the authors speculated that during MC, the relatively greater left-sided "happy" frontal activity is acting in a top-down fashion to dampen negative rumblings in the amygdala (although there is no absolutely no evidence for this). At both time points, the participants filled out questionnaires to asses state anxiety and approach/avoidance behaviors. Since the scores did not differ between the OV and MC phases, the authors suggested that the L>R frontal activity during MC was serving a useful purpose: to keep all those negative emotions in check. Note that none of the women in this study suffered from PMS. It would be important for their interpretation to test women with PMS and show that they do not have the L>R asymmetry during MC.

But let's look at the actual data. Basically, there was no asymmetry during OV, but greater R frontal activity during OV than MC [higher alpha = less activation].

Fig. 2 (Hwang et al., 2008a). The mean alpha power in the frontal regions at MC and OV phase. No [main] effect of hemispheric side and menstrual phase was noted. The phase by side analysis reveals a significant interaction (p = 0.004). Error bar represents the standard error of the mean. MEG alpha power is negatively related to the system activity.

Hmm.

Our results demonstrated that young females can express relatively greater resting right frontal activity during the OV as compared to MC phase. ... Estrogen has also been proposed to modulate the ‘arousal crescent’ of neurons in the female brain, improving assessment of the environment, threat anticipation, and preparing the organism for the stressful but ultimate goal of reproduction. It is contentious to speculate that higher right frontal activity could be a central correlate for achieving a higher readiness for fertility window.

It seems a little convoluted to postulate that greater activity in the so-called "withdrawal" system leads to a greater desire to mate.

Anyway. The more recent study of Hwang et al. (2008b) looked at MEG activity during a task where the female participants responded to pictures of faces with neutral, happy, or sad expressions and withheld responding to faces with fearful expressions. Here they looked at MEG activity evoked by the fearful face stimuli (evoked responses), rather than resting baseline activity. Although we don't get to see what the MEG data look like, results indicated that

the menstrual cycle was coupled with a shift of asymmetric lateralization of frontal activation across different menstrual phases. Evoked magnetic field activity in the time window 200-300ms (M1) and 300-450ms (M2) after stimulus onset demonstrated significant interactions between hemispheric side and menstrual phase. The right hemispheric dominance in periovulatory phase (OV) changed to left hemispheric dominance in menstrual (MC) phase. Significant association between the anxiety score and the left PFC activation was particularly observed in MC phase.

So in this study, there was a positive correlation between mean peak amplitude [thought to be a direct measure of activation] in the left PFC and state anxiety. Does this mean there's a failed attempt to regulate negative emotional responses to the fearful faces? It's not clear.

The take-home message?

It is conceivable to speculate that the dynamic change of left-right hemispheric preponderance may mediate automatic modulation and the emotional regulation across the menstrual cycle.

And thus ends the tale of the Female Flipping Brain on not a bang, but a whimper.

Footnote

1 But then again, I'm not very good at seeing and understanding the needs of other people, so I might come across as arrogant, impatient and insensitive to people that need some time to understand what I am talking about.

We previously reported that the trait/baseline prefrontal cortex (PFC) activity expresses a dynamic plasticity during female menstrual cycle. The shift of asymmetric lateralization of PFC baseline activity pinpoints a possible emotional regulation of negative affection. The current emotional Go/NoGo study aimed to investigate the state PFC responses of different menstrual phases during fear facial stimulation in fourteen healthy women. Our data disclosed that the menstrual cycle was coupled with a shift of asymmetric lateralization of frontal activation across different menstrual phases. Evoked magnetic field activity in the time window 200-300 ms (M1) and 300-450 ms (M2) after stimulus onset demonstrated significant interactions between hemispheric side and menstrual phase. The right hemispheric dominance in periovulatory phase (OV) changed to left hemispheric dominance in menstrual (MC) phase. Significant association between the anxiety score and the left PFC activation was particularly observed in MC phase. Our study revealed a plastic resilience of functional organization of human brain and a dynamic automaticity of inter-hemispheric synergism for possible adaptive regulation under the aversive confrontation in accordance with hormonal fluctuation during the menstrual cycle.

Friday, November 21, 2008

WOMEN may be fed up with being stereotyped as the chattier sex, but the cliche turns out to be true - in female-centric monkey groups at least. The gossipy nature of female macaques also adds weight to the theory that human language evolved to forge social bonds.

• A woman uses about 20,000 words per day while a man uses about 7,000

In a thoroughly researched series of posts from 2006, Mark Liberman explained there's no evidence at all for that claim:

I looked through the book to try to find the research behind the 20,000-vs.-7,000-words-per-day claim, and I looked on the web as well, but I haven't been able to find it yet. Brizendine also claims that women speak twice as fast as men (250 words per minute vs. 125 words per minute). These are striking assertions from an eminent scientist, with big quantitative differences confirming the standard stereotype about those gabby women and us laconic guys. The only trouble is, I'm pretty sure that both claims are false.

But back to the gossiping monkeys.

Many researchers think that language replaced grooming as a less time-consuming way of preserving close bonds in ever-growing societies.

Nathalie Greeno and Stuart Semple from Roehampton University in London hypothesised that if this was true then in species of animals with large social networks, such as macaques, vocal exchanges should be just as important as grooming.

The duo listened to a group of 16 female and eight2 male macaques living on Cayo Santiago island off Puerto Rico for three months. They counted the grunts, coos and girneys - friendly chit-chat between two individuals - while ignoring calls specific to the presence of food or a predator.

The team found that females made 13 times as many friendly noises as males. "The results suggest that females rely on vocal communication more than males due to their need to maintain the larger social networks," Greeno says.

This is not at all surprising, because the social structure of rhesus monkey troops is female-centric. As the authors (Greeno & Semple, 2008) explain in their paper:

In female-bonded primate species, adult females spend significantly more time involved in grooming than adult males and also devote a much higher proportion of their time to same-sex rather than mixed-sex grooming interactions.

And why are these monkey vocalizations considered "gossip"? The NewScientist article continues:

Females were also much more likely to chat to other females than to males. Greeno suggests this is because female macaques form solid, long-lasting bonds as they stay in the same group for life and rely on their female friends to help them look after their offspring. In contrast, males, who rove between groups throughout their life, chatted to both sexes equally (Evolution and Human Behavior, DOI: 10.1016/j.evolhumbehav.2008.09.002).

So here we have the nonverbal vocalizations of female monkeys as a precursor to the "chattier" nature of female humans...

1 This quote was from the original version of Louann Brizendine's book, The Female Brain.

2 The original paper said there were only 7 male monkeys, or to be precise: 16 adult females and 7 adult males. One set of analyses did correct for this unequal number. There were also an unknown number of juvenile monkeys, although the article did not say how many. Data were collected only from the adults, with separate analyses examining vocalizations directed towards all monkeys vs. vocalizations directed towards adults only.

INTP - The Thinkers

The logical and analytical type. They are especialy attuned to difficult creative and intellectual challenges and always look for something more complex to dig into. They are great at finding subtle connections between things and imagine far-reaching implications.

They enjoy working with complex things using a lot of concepts and imaginative models of reality. Since they are not very good at seeing and understanding the needs of other people, they might come across as arrogant, impatient and insensitive to people that need some time to understand what they are talking about.

Analysis

This show what parts of the brain that were dominant during writing.**

As you can see in the figure above, this blog is heavily dependent on the frontal lobes (bilaterally) with little to no contribution from the rest of the brain.

Crackpot - INTJ

I mean, you're pretty damn clever and you know it. You love to flaunt your potential. Heard the word "arrogant" lately? How about "jerk?" Or perhaps they only say that behind your back.

That's right. I know I can say this cause you're not going to cry. You're not exactly the most emotional person. You'd rather spend time with your theoretical questions and abstract theories than with other people.

Ever been kissed? Ever even been on a date? Trust me, your inflated ego is a complete turnoff with the opposite sex and I am telling you, you're not that great with relationships as it is. You're never going to be a dude or chick magnet, purely because you're more concerned with yourself than others. Meh. They all hate you already anyway.

How about this- "stubborn?" Hrm? Heard that lately? All those facts which don't fit your theories must just be wrong, right? I mean, really, the vast amounts of time you spend with your head in the clouds...you're just plain strange.

INTJ - The Scientists

The long-range thinking and individualistic type. They are especially good at looking at almost anything and figuring out a way of improving it - often with a highly creative and imaginative touch. They are intellectually curious and daring, but might be pshysically hesitant to try new things.

The Scientists enjoy theoretical work that allows them to use their strong minds and bold creativity. Since they tend to be so abstract and theoretical in their communication they often have a problem communcating their visions to other people and need to learn patience and use conrete examples. Since they are extremly good at concentrating they often have no trouble working alone.

The Analysis, however, indicates that the exact same brain regions were dominant during writing as when this was an INTP blog...

...the interaction between the internet and psychosis that explored online communities that may be focused on delusional beliefs or comprised almost entirely of people who are having psychotic experiences.

The NYT article, Sharing Their Demons on the Web, describes a number of sites devoted to things like mind control and "gang stalking." The visitors reinforce each other's pathology, but also find some much needed support:

Dr. Bell and some other mental health professionals say that even if the users of such sites are psychotic, forging an online connection to others and being told — perhaps for the first time — “you are not crazy” could actually have a positive effect on their illnesses.

“We know, for example, that things like social support, all of these positive social aspects are very good for people’s mental illness,” Dr. Bell said. “I wouldn’t say it’s entirely and completely positive, but it can be positive.”

Huntington's disease is an inherited, autosomal dominant, neurodegenerative disorder. Although primarily viewed as a movement disorder characterized by uncontrollable body movements (chorea), there is also a marked decline in cognitive abilities, often accompanied by psychiatric issues as well.

It's a terrible disease that typically onsets in middle age. A heartbreaking New York Times article, Facing Life With a Lethal Gene, follows a 23 year old woman who decides to get tested and finds out she carries the gene. Her grandfather had the disease, meaning that her mother, who did not know her own genetic status, was doomed to develop HD.

As stated in this Lancet review article (Walker, 2007),

The mutant protein in Huntington’s disease—huntingtin—results from an expanded CAG repeat leading to a polyglutamine strand of variable length at the N-terminus. Evidence suggests that this tail confers a toxic gain of function.

The defective protein causes cell death in various brain regions, particularly in the striatum (caudate and putamen), perhaps due to an excitotoxic mechanism (Sánchez et al., 2008). As Beste et al. (2008) explain in their new J Neurosci paper,

Excitotoxicity describes cell death that results from the activation of excitatory amino acid receptors. In HD, voltage-dependent NMDA receptors are assumed to be more receptive to endogenous levels of glutamate; thus glutamatergic neurotransmission is increased, leading to excitotoxic cell death.

The medium spiny neurons in the striatum are especially affected. Given all this neurodegeneration and the concomitant decline in motor function and cognition, it was surprising to see a paper reporting an enhanced perceptual/cognitive ability. But that's what Beste et al. (2008) observed. In their study, patients with HD, pre-symptomatic carriers, and controls participated in an auditory processing experiment while EEG data were recorded. The task consisted of categorizing the duration of pure tones as either long (400 ms) or short (200 ms). The tones were of different frequencies and different probabilities, but this was irrelevant to the task. This difference in probability, however, results in different patterns of brain waves to the common ("standard") and rare ("deviant") tones. Specifically, the authors looked at the mismatch negativity (MMN) component associated with auditory sensory memory, and the P3a component associated with attention. These waves were derived by averaging together many trials of the task, which produces event-related potentials (ERPs).

Behaviorally speaking, the participants with HD were faster and more accurate on the auditory task.

Figure 1 (Beste et al., 2008). Behavioral data. A, Mean reaction time (error bars indicate SEM) of the control, the presymptomatic (pHD), and the symptomatic (HD) group for the standard and deviant stimuli. B, Mean error rates (error bars indicate SEM) of the control, the presymptomatic (pHD), and the symptomatic (HD) group for the standard and deviant stimuli.

For the ERPs, responses to the standard tones were subtracted from responses to the deviant tones, producing a so-called "difference wave." The MMN can be seen between 100-250 ms after stimulus presentation and the P3a can be seen between 300 and 500 ms post-stimulus. A later wave (the reorienting negativity, or "RON") was seen between 400 and 600 ms.

adapted from Figure 2 (Beste et al., 2008).Neurophysiological data (difference waves). For all electrodes shown, the time course from 200 ms before tone onset until 1100 ms beyond tone presentation is given. Red lines denote the ERP time course of the HD group, orange lines of the pHD group, and green lines of the control group.

The HD group showed a significant increase in MMN compared to the pHD and control groups. On the other hand, although the P3a looked smaller in HD participants, the difference was not significant. The later RON wave was enhanced in the HD group, however. The authors suggest:

The results show that specific cognitive functions, namely auditory sensory memory (reflected by the MMN) and reorientation of attention (reflected by the RON) are not deteriorated and can even be enhanced in late stage HD. Moreover, the results suggest that superiority in these functions emerge primal in the late stage of this disease, because pHDs performed worse.

I should point out that on nearly every other neuropsychological test (i.e., word fluency, digit span, Stroop interference, immediate and delayed memory), the subjects with HD were extremely impaired. Then what is the mechanism for the enhancement of auditory abilities?

...the specific dependence of the MMN on the corticostriatal NMDA system underlies this dissociation of performance in HD as well as the enhancement and acceleration of the MMN. The NMDA-receptor system has been found to modulate the MMN (Javitt et al., 1996).

. . .

The observation that the reorientation of attention (reflected by the RON) was also increased in the HD group accords with the enhanced behavioral performance in the relevant task...

Although the primary effects of neurodegenerative diseases like HD might be largely confined to certain cell populations in restricted areas of the brain, these changes can affect cognitive and motor systems at multiple levels of the brain. In most cases, the pathological alterations of neural systems result in a deterioration of cognitive functions. However, as shown in the present study, a pathogenic increase in responsiveness of a transmitter system can increase cognitive functions if these functions selectively depend on this neural system, whereas other cognitive functions are deteriorated.

What is the clinical relevance of this finding? It's not clear. But the results revealed an unexpected and striking dissociation of cognitive abilities in patients with Huntington's disease.

CHICAGO (Reuters) – Brain scans of teens with a history of aggressive bullying behavior suggest that they may actually get pleasure out of seeing someone else in pain...

While this may come as little surprise to those who have been victimized by bullies, it is not what the researchers expected, Benjamin Lahey of the University of Chicago, who worked on the study, said in a telephone interview.

"The reason we were surprised is the prevailing view is these kids are cold and unemotional in their aggression," said Lahey, whose study appears in the journal Biological Psychology.

"This is looking like maybe they care very much," said Lahey, who worked on the study with Jean Decety, also of the University of Chicago.

The researchers compared eight boys ages 16 to 18 with aggressive conduct disorder2 to a group of eight adolescent boys with no unusual signs of aggression.

. . .

They showed both groups video clips of someone inflicting pain on another person and tracked brain activity with ... fMRI.

In the aggressive teens, areas of the brain linked with feeling rewarded -- the amygdala and ventral striatum -- became very active when they observed pain being inflicted on others.

Each animation displayed one or two persons whose right hands or right feet were visible but not their faces (see Fig. 1). ... These 96 stimuli belonged to four categories (24 each) of pain and involved person types, including:

1. Only one person is in a painful situation caused by accident, e.g., a person dropping a heavy bowl on her hand (PCA, pain caused by accident).

2. Only one person is involved in a non-painful situation, e.g., opening a door (NPS, no pain situation).

3. One person is in a painful situation caused by another, e.g., stepping purposely on someone's toe (PCO, pain caused by other).

4. One person is in a painful situation at first but this pain is alleviated by the other, e.g., helping another get his or her hand out of a door (APO, alleviated pain by other).

The 8 boys in the smallish CD group were among the "worst offenders" in a larger group of 127 adolescents with ADHD (all enrolled in a longitudinal study). Over the course of 9 years, they displayed a mean of 7.5 aggressive symptoms (including starting fights; bullying using a weapon; theft with confrontation of the victim; physical cruelty to people; cruelty to animals; and forced sex). The 8 control boys, of course, did not have CD and were much less likely to have ADHD (always a confound because of co-morbidity).

Parents completed a rating scale that quantified three "socioemotional dispositions":

Prosociality is defined by sympathetic concern for others, helping and sharing, respect for social rules, and guilt over misdeeds.

Daring is defined by the descriptors of daring, brave, and adventurous, and by enjoyment of risky and loud activities and rough games and sports. It is ... a robust predictor of future criminal offending and is similar to the construct of sensation seeking.

Children rated high on negative emotionality are easily and intensely upset by frustrations, threats, and losses.

There was also a sadism measure, which consisted of these items:

enjoys bothering or hurting other children

thinks it's funny when other children are upset

likes to scare other children

thinks it would be fun to watch two dogs fight

During the fMRI scanning session the participants viewed the four different stimulus types in separate blocks of trials. No response was required. One of the major findings is illustrated below.

Fig. 1 bottom (from Decety et al., 2008). Selective activation of the ACC, aMCC and PAG overlaid onto a sagittal MRI section of the MNI brain [for the contrast pain caused by accident vs. non-painful situations.]Activation of areas that belong to the pain matrix (including the anterior insula and somatosensory cortex, not shown here) was stronger in the adolescents with CD. Note that the amygdala and ventral striatum were also strongly activated in the CD group.

OK, so the kids with CD apparently found watching the Hah-Ha! stimuli to be more "rewarding" than did the control kids (based on greater responses in the amygdala4 and ventral striatum). HOWEVER, the CD kids also showed greater "empathy for pain." This is based on the authors' past interpretation of what greater activity in the pain matrix signifies.5 Pain ratings for each of the stimuli were obtained after scanning, and these scores did not differ between the control and CD boys.

So what does it all mean? Taken together with results from the pain caused by others condition [not discussed here] the authors conclude:

Overall, our results suggest a complex relation between the neural correlates of empathy and CD. The functional MRI data seem to indicate that adolescents with CD are at least as responsive to the pain of others as the adolescents without CD. The fact that activation of the posterior insula, somatosensory cortex, and PAG were involved in the observation of others in painful situations supports such an interpretation.

However, when observing pain intentionally caused by another there was no activation in adolescents with CD, in the neural regions that contribute to self-regulation and metacognition (including moral reasoning), such as the DLPFC, PCC, TPJ, dorsal and medial ACC and lateral OFC. This pattern stands in contrast with that of the control group and a previous study with typically developing children.

And, of course, further studies with larger groups are needed.

Footnotes

1 A fictional cartoon character did not really participate in a research study, but the actual participants were older boys who fit a similar profile (broadly speaking).

Because youth with aggressive conduct disorder (CD) often inflict pain on others, it is important to determine if they exhibit atypical empathic responses to viewing others in pain. In this initial functional magnetic resonance imaging (fMRI) study, eight adolescents with aggressive CD and eight matched controls with no CD symptoms were scanned while watching animated visual stimuli depicting other people experiencing pain or not experiencing pain. Furthermore, these situations involved either an individual whose pain was caused by accident or an individual whose pain was inflicted on purpose by another person. After scanning, participants rated how painful the situations were. In both groups the perception of others in pain was associated with activation of the pain matrix, including the ACC, insula, somatosensory cortex, supplementary motor area and periaqueductal gray. The pain matrix was activated to a significantly greater extent in participants with CD, who also showed significantly greater amygdala, striatal, and temporal pole activation. When watching situations in which pain was intentionally inflicted, control youth exhibited signal increase in the medial prefrontal cortex, lateral orbitofrontal cortex, and right temporo-parietal junction, whereas youth with CD only exhibited activation in the insula and precentral gyrus. Furthermore, connectivity analyses demonstrated that youth with CD exhibited less amygdala/prefrontal coupling when watching pain inflicted by another than did control youth. These preliminary findings suggest that youth with aggressive CD exhibit an atypical pattern of neural response to viewing others in pain that should be explored in further studies.

El Día de los Muertos, held on November 2nd is an important religious holiday in Mexico. Also called All Souls Day, it is an occasion marked by festive celebrations to honor the dead. Cemeteries are cleaned and decorated, special food and candies cooked, and home altars are designed in homage to ones ancestors. It is a day of joyous remembrance, not of sadness. The special songs, poems, foods and Day of the Dead art created for El Día de los Muertos reflect this outlook.

Fusing Halloween, All Soul's Day, and Election Day, one comes up with The Day of the unDead Politicians...

Although it's old news now, among the most infamous of the Zombie McCain genre were those of the prominent professional photographer, Jill Greenberg (example above). Although she has removed most of the doctored images from The Manipulator, the front page (at present) still includes this unflattering portrait from her photo shoot with McCain for The Atlantic.

About Me

Born in West Virginia in 1980, The Neurocritic embarked upon a roadtrip across America at the age of thirteen with his mother. She abandoned him when they reached San Francisco and The Neurocritic descended into a spiral of drug abuse and prostitution. At fifteen, The Neurocritic's psychiatrist encouraged him to start writing as a form of therapy.